FDA Approves Mitapivat (AQVESME) for Non-Transfusion-Dependent Alpha- and Beta-Thalassemia

Announced by parent company Agios on December X, 2025, the US Food and Drug Administration (FDA) has approved mitapivat under the brand name AQVESME for the treatment of anemia in adults with alpha- or beta-thalassemia.1

"Despite its severity, treatments [for thalassemia] have historically been limited, leaving some patients without any options," Hanny Al-Samkari, MD, Peggy S. Blitz Endowed Chair in Hematology/Oncology at Massachusetts General Brigham Cancer Institute and associate professor at Harvard Medical School, said in a statement. "The ENERGIZE and ENERGIZE-T Phase 3 trial results demonstrate that AQVESME can help address anemia, fatigue, and the need for regular transfusions - key challenges of the disease."1

Mitapivat is a small-molecule oral activator of pyruvate kinase R (PKR), which is involved in maintaining the energy, health, and longevity of red blood cells. Mitapivat improves red blood cell survival in sickle cell disease by increasing ATP and diminishing sickling via decreases in 2,3-diphosphoglycerate.2

The FDA’s decision was based on results from the phase 3 ENERGIZE and ENERGIZE-T trials. ENERGIZE was a double-blind, randomized, placebo-controlled trial conducted across 70 hospitals in 18 countries globally. For inclusion, patients had to be ≥18 years with non-transfusion-dependent alpha- and beta-thalassemia and hemoglobin concentrations of ≤10 g/dL.3

In ENERGIZE, patients were randomly assigned in a 2:1 ratio to either mitapivat or placebo, both of which were administered at 100 mg orally twice a day for 24 weeks. The primary endpoint was the change in hemoglobin response from baseline.3

Ultimately, 194 patients were enrolled, with 130 assigned to mitapivat and 64 to placebo. A total of 7 patients receiving mitapivat and 1 receiving placebo discontinued treatment. 55 patients in the mitapivat group had a hemoglobin response, compared to 1 in the placebo group (least-squares mean difference, 41%; 95% CI, 32-50; P <.0001). Adverse events were reported in 107 patients in the mitapivat arm versus 63 in the placebo arm, with the most common being headache, initial insomnia, nausea, and upper respiratory tract infection. No deaths were reported.3

The ENERGIZE-T trial was a global, double-blind, randomized, placebo-controlled study to investigate the efficacy and safety of mitapivat versus placebo in adults with transfusion-dependent alpha- or beta-thalassemia. Investigators randomly assigned patients ≥18 years in a 2:1 ratio to mitapivat 100 mg or placebo twice daily for 48 weeks.4

ENERGIZE-T's primary endpoint was transfusion reduction response (TRR), defined as a ≥50% reduction in transfused red blood cell (RBC) units and a reduction of ≥2 units of transfused RBCs in any consecutive 12-week period compared with baseline. Key secondary endpoints were TRR2, a ≥50% reduction from baseline in transfused RBC units in any consecutive 24-week period, TRR3, a ≥33% reduction from baseline in transfused RBC units in weeks 13-48, and TRR4, a ≥50% reduction from baseline in transfused RBC units at weeks 13-48.4

A total of 258 patients were randomized, with 171 assigned to mitapivat and 87 to placebo. A TRR was achieved in 30.4% of patients in the mitapivat arm versus 12.6% in the placebo arm. Additionally, statistically significant reductions in transfusion burden were demonstrated by all key secondary endpoints: 13.5% versus 2.3% achieved TRR2; 14.6% versus 1.1% achieved TRR3; 7.6% versus 1.1% achieved TRR4.4

"Today is a landmark moment for the thalassemia community, bringing forward an innovative, disease-modifying oral medicine to address the urgent needs of people living with this devastating rare blood disorder," Brian Goff, chief executive officer of Agios, said in a statement. "With this approval, AQVESME becomes the only medicine indicated for the treatment of anemia in both non-tranfusion-dependent and transfusion-dependent alpha- or beta-thalassemia."1

References

1. Agios Pharmaceuticals. US FDA Approves Agios' AQVESME (mitapivat) for the Treatment of Anemia in Adults with Alpha- or Beta-Thalassemia. December 23, 2025. Accessed December 24, 2025. https://investor.agios.com/news-releases/news-release-details/us-fda-approves-agios-aqvesmetm-mitapivat-treatment-anemia

2. Agios Pharmaceuticals. Agios Announces Topline Results from RISE UP Phase 3 Trial of Mitapivat in Sickle Cell Disease. November 19, 2025. Accessed December 5, 2025. https://investor.agios.com/news-releases/news-release-details/agios-announces-topline-results-rise-phase-3-trial-mitapivat

3. Taher AT, Al-Samkari H, Aydinok Y, et al. Mitapivat in adults with non-transfusion-dependent α-thalassaemia or β-thalassaemia (ENERGIZE): A phase 3, International, randomised, double-blind, placebo-controlled trial. The Lancet. 2025;406(10498):33-42. doi:10.1016/s0140-6736(25)00635-x

4. Cappellini MD, Sheth S, Taher AT, et al. Energize-T: A global, phase 3, double-blind, randomized, placebo-controlled study of mitapivat in adults with transfusion-dependent alpha- or beta-thalassemia. Blood. 2024;144(Supplement 1):409-409. doi:10.1182/blood-2024-200867